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Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19.
Kahn, Robin; Schmidt, Tobias; Golestani, Karan; Mossberg, Anki; Gullstrand, Birgitta; Bengtsson, Anders A; Kahn, Fredrik.
  • Kahn R; Department of Clinical Sciences Lund, Section of Pediatrics, Lund University, Lund, Sweden.
  • Schmidt T; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
  • Golestani K; Skåne University Hospital, Lund and Malmö, Sweden.
  • Mossberg A; Department of Clinical Sciences Lund, Section of Pediatrics, Lund University, Lund, Sweden.
  • Gullstrand B; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
  • Bengtsson AA; Skåne University Hospital, Lund and Malmö, Sweden.
  • Kahn F; Department of Clinical Sciences Lund, Section of Pediatrics, Lund University, Lund, Sweden.
J Leukoc Biol ; 109(1): 115-120, 2021 01.
Article in English | MEDLINE | ID: covidwho-1188015
ABSTRACT
The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COVID-19 (n = 6) and sepsis (n = 3) were included at Skåne University Hospital, Sweden. Healthy controls were also recruited (n = 5). Cytokines were measured in COVID-19 and sepsis patients using an Immulite immunoassay system. PBMCs were cultured with brefeldin A to allow cytokine accumulation. In parallel, LPS was used as an activator. Cells were analyzed for cytokines and surface markers by flow cytometry. High levels of IL-6 and measurable levels of IL-8 and TNF, but not IL-1ß, were observed in COVID-19 patients. Monocytes from COVID-19 patients had spontaneous production of IL-1ß and IL-8 (P = 0.0043), but not of TNF and IL-6, compared to controls. No spontaneous cytokine production was seen in lymphocytes from either patients or controls. Activation with LPS resulted in massive cytokine production by monocytes from COVID-19 patients and healthy controls, but not from sepsis patients. Finally, monocytes from COVID-19 patients produced more IL-1ß than from healthy controls (P = 0.0087) when activated. In conclusion, monocytes contribute partly to the ongoing hyperinflammation by production of IL-1ß and IL-8. Additionally, they are responsive to further activation. This data supports the notion of IL-1ß blockade in treatment of COVID-19. However, the source of the high levels of IL-6 remains to be determined.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Monocytes / Cytokines / SARS-CoV-2 / COVID-19 Type of study: Observational study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: J Leukoc Biol Year: 2021 Document Type: Article Affiliation country: JLB.5COVBCR0720-310RR

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Monocytes / Cytokines / SARS-CoV-2 / COVID-19 Type of study: Observational study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: J Leukoc Biol Year: 2021 Document Type: Article Affiliation country: JLB.5COVBCR0720-310RR